Is MEFV p.Ser242= (c.726C>T) pathogenic?

MEFV p.Ser242= (c.726C>T) is classified Conflicting classifications of pathogenicity in MEFV (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2025-06-27). Very rare (popmax 0.00223%, eas); Associated with autoinflammatory syndrome.

What condition is associated with MEFV p.Ser242= (c.726C>T)?

MEFV p.Ser242= (c.726C>T) is associated with autoinflammatory syndrome, familial Mediterranean fever (ClinVar).

How common is MEFV p.Ser242= (c.726C>T) in the general population?

MEFV p.Ser242= (c.726C>T) is very rare (popmax 0.00223%, eas) (gnomAD).

MEFV p.Ser242=

c.726C>T · rs104895127 · VCV97542

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Conditions

autoinflammatory syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.6	GERP -2.3, phastCons 0.93
Overall
CADD	4.594	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,894 alleles

Filtering AF 0.000542% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000428%

Overall 0.000867% 14/1,614,118 alleles · very rare exomes 13/1,461,892 · genomes 1/152,226 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,894
Remaining individualsnot grpmax-eligible	0.0016%	62,490
European (non-Finnish)	0.00102%	98,336

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: MEFV
Protein: p.Ser242=
Coding: c.726C>T
MANE Select: NM_000243
dbSNP: rs104895127
Type: single nucleotide variant
Location: chr16:3254342 (GRCh38)
Gene constraint: LOEUF 1.147 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 73.64 · 11 PDB
Residue 242: a modified residue (phosphoserine); a UniProt-annotated variant site (in paand; results in constitutive inflammasome activation; increased pycard/asc specks formation; increased caspase-1 activation and il1b production; loss of s-242 phosphorylation; loss of interaction with 14-3-3 proteins)

Full MEFV gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

autoinflammatory syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: familial Mediterranean fever

Similar variants

MEFV p.Ser242Arg Pathogenic/Likely pathogenic ★★ same residue
MEFV p.Ser242Gly Likely pathogenic ★ ⚠ same residue
MEFV p.Ser242Thr Uncertain significance ★ ⚠ same residue
MEFV p.Arg761His Pathogenic/Likely pathogenic ★★ ⚠ same condition
MEFV p.Val726Ala Pathogenic/Likely pathogenic ★★ ⚠ same condition
MEFV c.*845C>T Uncertain significance ★★ same condition
MEFV p.Ala193Thr Uncertain significance ★★ ⚠ same condition
MEFV p.Ala2Gly Uncertain significance ★★ ⚠ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/mefv-p-ser242 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown